Metastatic CancerPhase 1FORTITUDENCT03852511
First in Human Study of NG-350A (an Oncolytic Adenoviral Vector Which Expresses an Anti-CD40 Antibody)
A Phase 1 study testing NG-350A in people with Metastatic Cancer and Epithelial Tumor, run by Akamis Bio at 5 sites in United States.
Trial summary
This study will evaluate the safety, tolerability and preliminary efficacy and also pharmacokinetics, immunogenicity and other pharmacodynamic effects to elucidate the mechanism of action of NG-350A, either alone or in combination with a check point inhibitor, in patients with advanced or metastatic 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-350A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 5 sitesUnited States
- Study dates
- 19 Feb 2019to 4 Feb 2022
- 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
- Provide written informed consent to participate
- Aged 18 years or over
- Have one of eleven histologically or cytologically confirmed metastatic or advanced carcinomas or adenocarcinomas that have progressed after at least one line of systemic therapy and are incurable by local therapy
- Tumour types eligible are: UC, SCCHN, MSI high/dMMR cancer, NSCLC, uterine/endometrial cancer, cervical cancer, oesophageal cancer, gastric cancer, cutaneous squamous cell carcinoma, HCC and TNBC
- Additional tumour type specific criteria:
- UC: carcinoma of the renal pelvis, ureter, bladder, or urethra that showed predominantly transitional-cell features on histologic testing
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- SCCHN with oropharyngeal cancer: known HPV p16 status
- MSI-high/dMMR cancer: MSI-high/dMMR status must be confirmed by an approved test
- NSCLC: either squamous or non-squamous histology
- Gastric cancer: gastric or gastroesophageal junction adenocarcinoma
- All patients enrolled in combination therapy cohorts with check point inhibitor (dose escalation and efficacy expansion phases) must have received prior treatment with a PD 1/PD-L1 inhibitor therapy (prior PD-1/PD-L1 may have been given as monotherapy or combination therapy)
- In combination dose-escalation, patients may have received a PD 1/PD L1 inhibitor as part of any prior line of therapy (additional criteria apply when this is the most recent line of therapy - see below)
- In dose expansion cohorts, patients must have been treated with a PD 1/PD-L1 inhibitor as part of their most recent treatment
- For all patients who received PD-1/PD-L1 inhibitor therapy as part of their most recent line of treatment (includes dose-escalation and all patients in dose-expansion), this must have been for a minimum of 6 weeks and maximum of 6 months, with best response of SD or PD - Patients with PD following treatment with a PD-1/PD-L1 inhibitor as their most recent therapy must have a <50% increase in disease burden
- 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 for biopsy by the Investigator, and patient willing to consent to tumour biopsies
- Ability to comply with study procedures in the Investigator's opinion
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Predicted life expectancy of 6 months or more
- Adequate lung reserve
- Adequate renal function
- Adequate hepatic function
- Adequate bone marrow function
- Coagulation profile within the normal range (international normalized ratio ≤1.5)
- 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
- Active viral disease or positive test for hepatitis B virus using hepatitis B surface antigen test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection. Positive test for HIV or AIDS
- 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 systemic immunosuppressive treatment
- Patients with vitiligo, type I diabetes mellitus, asthma/atopy, residual hypothyroidism due to autoimmune disease (which only requires hormone replacement therapy), or conditions not expected to recur in the absence of an external trigger are permitted to enrol providing they comply with the other eligibility criteria relating to renal function. Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed
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- Treatment with any live, live attenuated or COVID-19 vaccine in the 28 days before the first dose of NG 350A
- COVID-19 vaccines known not to be based on an adenoviral vector (e.g. mRNA vaccines) are not subject to the 28-day exclusion (see exclusion criterion 7)
- Treatment with any other vaccine (including known non-adenoviral COVID-19 vaccines) in the 7 days before first dose of NG-350A
- 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 (clinically suspected or radiographic evidence)
- Infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment
- Myocardial infarction, stroke or other significant cardiovascular or cerebrovascular event in the 12 months before the first dose of study treatment
- Pulmonary embolism, deep vein thrombosis, or other uncontrolled thromboembolic event in the 12 months before the first dose of study treatment, or current treatment with therapeutic or prophylactic anticoagulation therapy
- Grade 3 or 4 gastrointestinal bleeding (or risk factors for gastrointestinal bleeding) or haemoptysis in the 3 months before first dose of study treatment, or any history of bleeding requiring an investigative procedure (e.g. endoscopy), transfusion or hospitalisation in the 12 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 (e.g. an initial increase in tumour size that may lead to intestinal, airway or ureter obstruction, or penetrating tumour infiltration of major blood vessels, or other hollow organs potentially at risk of perforation)
- Use of the following prior therapies/treatments:
- Treatment with any other anti CD40 antibody 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 or radiation therapy in the 14 days before the first dose of study treatment
- Bisphosphonate therapy or treatment with Receptor Activator of Nuclear factor Kappa-B (RANK)-ligand inhibitors for metastatic bone disease is permitted
- All toxicities attributed to prior anti-cancer therapy (including radiation therapy) other than alopecia must have resolved to Grade 1 or baseline before the first dose of study treatment. Patients with toxicities (other than renal toxicities) attributed to prior anti-cancer therapy that are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum-based therapy, are permitted to enrol
- Treatment with the antiviral agents ribavirin, adefovir, lamivudine or cidofovir within 7 days prior to the first dose of study treatment; or pegylated interferon (PEG-IFN) in the 14 days before the first dose of study treatment
- Known allergy/immune-related adverse reactions to NG-350A transgene or immune checkpoint inhibitor products or formulation; severe hypersensitivity to another monoclonal antibody
- Other prior malignancy active within the previous 3 years, except for local or organ confined early-stage cancer that has been definitively treated with curative intent, does not require ongoing treatment, has no evidence of residual disease and has a negligible risk of recurrence and is therefore unlikely to interfere with the primary and secondary endpoints of the study, including response rate and safety
- Symptomatic brain metastases or any leptomeningeal metastases that are symptomatic and/or require treatment. Patients with brain metastases are eligible if these have been treated (surgery, radiotherapy). Both surgery and or radiotherapy must have been completed at least 2 weeks before first dose of study treatment. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalent) for at least 2 weeks before the first dose of study treatment
- 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
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Colorado
Aurora, Colorado, 80045
Cleveland Clinic
Cleveland, Ohio, 44195
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center (MSKCC)
New York, New York, 10038
University of California, Los Angeles (UCLA)
Santa Monica, California, 90404
About this study
Official title: A Multicentre, Open Label, Non-randomised First in Human Study of NG-350A (Monotherapy), and NG-350A With a Check Point Inhibitor in Patients With Metastatic or Advanced Epithelial Tumours
This study will evaluate the safety, tolerability and preliminary efficacy and also pharmacokinetics, immunogenicity and other pharmacodynamic effects to elucidate the mechanism of action of NG-350A, either alone or in combination with a check point inhibitor, in patients with advanced or metastatic epithelial tumours.
Read the detailed description
Phase Ia of this study is a dose escalation phase, investigating NG-350A administration by intravenous (IV) infusion, either alone or in combination with a check point inhibitor. Phase Ib of this study comprises of a Combination Dose Efficacy Expansion with NG-350A in combination with a check point inhibitor.
- Conditions
- Metastatic Cancer, Epithelial Tumor
- Being tested
- NG-350A
- Keywords
- metastatic; epithelial; virus; advanced
- Medical subject headings
- Neoplasm Metastasis, Carcinoma, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NG-350ABiological
NG-350A is oncolytic adenoviral vector which expresses a full length agonist anti-CD40 antibody at the site of virus replication.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous | Experimental | Patients will receive three single doses of NG-350A by IV infusion, followed by multiple cycles of check point inhibitor treatment. Receives: Biological: NG-350A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events, serious adverse events, adverse events meeting protocol-defined DLT criteria, severe adverse events, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death.
Characterise the safety and tolerability of NG-350A, in combination with a check point inhibitor, by reviewing reported Adverse Events (AEs) and Serious Adverse Events (SAEs).
Measured: Throughout study to end of study treatment visit (Week 24 or +30 days after last study drug dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2019
- Study start19 Feb 2019
- Primary completion4 Feb 2022
- Study completion4 Feb 2022
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
- Model description
- Patients in Part A will receive a single cycle of NG-350A study treatment, with three single doses on Days 1, 3 and 5 by IV infusion. Patients in Part B will receive a single cycle of NG-350A study treatment, with three single doses on Days 1, 3 and 5 by IV infusion, followed by up to 8 cycles of a check point inhibitor.
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akamis Bio
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Aung Naing, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03852511
- Sponsor's protocol ID
- NG-350A-01
- Acronym
- FORTITUDE
- Status last verified
- Jun 2022
- First submitted
- 11 Feb 2019
- Last updated
- 24 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- 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 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Open Label, Non-randomised First in Human Study of NG-350A (Monotherapy), and NG-350A With a Check Point Inhibitor in Patients With Metastatic or Advanced Epithelial Tumours
- ClinicalTrials.gov ID
- NCT03852511
- Acronym / sponsor ID
- FORTITUDE / NG-350A-01
- Conditions
- Metastatic Cancer, Epithelial Tumor
- Keywords
- metastatic; epithelial; virus; advanced
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Akamis BioIndustry (pharma, biotech, devices)
- Study start
- 19 Feb 2019 (actual)
- Primary completion
- 4 Feb 2022 (actual)
- Study completion
- 4 Feb 2022 (actual)
- First posted
- 25 Feb 2019 (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 study will evaluate the safety, tolerability and preliminary efficacy and also pharmacokinetics, immunogenicity and other pharmacodynamic effects to elucidate the mechanism of action of NG-350A, either alone or in combination with a check point inhibitor, in patients with advanced or metastatic epithelial tumours.
Detailed description
Phase Ia of this study is a dose escalation phase, investigating NG-350A administration by intravenous (IV) infusion, either alone or in combination with a check point inhibitor. Phase Ib of this study comprises of a Combination Dose Efficacy Expansion with NG-350A in combination with a check point inhibitor.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients in Part A will receive a single cycle of NG-350A study treatment, with three single doses on Days 1, 3 and 5 by IV infusion. Patients in Part B will receive a single cycle of NG-350A study treatment, with three single doses on Days 1, 3 and 5 by IV infusion, followed by up to 8 cycles of a check point inhibitor.
| Arm | Type | Receives |
|---|---|---|
| Intravenous | Experimental | Biological: NG-350APatients will receive three single doses of NG-350A by IV infusion, followed by multiple cycles of check point inhibitor treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Provide written informed consent to participate
- Aged 18 years or over
- Have one of eleven histologically or cytologically confirmed metastatic or advanced carcinomas or adenocarcinomas that have progressed after at least one line of systemic therapy and are incurable by local therapy
- Additional tumour type specific criteria:
- All patients enrolled in combination therapy cohorts with check point inhibitor (dose escalation and efficacy expansion phases) must have received prior treatment with a PD 1/PD-L1 inhibitor therapy (prior PD-1/PD-L1 may have been given as monotherapy or combination therapy)
Key exclusion criteria (29 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
- Active viral disease or positive test for hepatitis B virus using hepatitis B surface antigen test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection. Positive test for HIV or AIDS
- 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 systemic immunosuppressive treatment
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-350ANG-350A is oncolytic adenoviral vector which expresses a full length agonist anti-CD40 antibody at the site of virus replication. | Biological | Intravenous |
Primary outcome
Incidence of adverse events, serious adverse events, adverse events meeting protocol-defined DLT criteria, severe adverse events, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death.
Time frame: Throughout study to end of study treatment visit (Week 24 or +30 days after last study drug dose)
Characterise the safety and tolerability of NG-350A, in combination with a check point inhibitor, by reviewing reported Adverse Events (AEs) and Serious Adverse Events (SAEs).
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 Jun 2022.
- 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.
Aung Naing, MD principal investigator
M.D. Anderson Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NG-350A in people with Metastatic Cancer and Epithelial Tumor, run by Akamis Bio at 5 sites in United States.
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 25 inclusion and 29 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 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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, serious adverse events, adverse events meeting protocol-defined DLT criteria, severe adverse events, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death. (time frame: Throughout study to end of study treatment visit (Week 24 or +30 days after last study drug dose)). 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 NCT03852511, 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 Jun 2022.