First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector (STAR)
Primary Purpose
Metastatic Cancer, Epithelial Tumor
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NG-641
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Cancer focused on measuring metastatic; epithelial; virus; advanced; PsiOxus
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically documented advanced or metastatic epithelial cancer that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available
- Provide written informed consent to participate
- Aged 18 years or over
- Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies
- ECOG performance status 0 or 1
- Predicted life expectancy of 6 months or more
- Ability to comply with study procedures in the Investigator's opinion
- Adequate lung reserve
- Adequate renal function
- Adequate hepatic function
- Adequate bone marrow function
- Coagulation profile within normal range and International Normalised Ratio ≤1.5, as appropriate
- Meeting reproductive status requirements
- Phase Ia - Dose Optimisation Phase only: at least one measurable site of disease according to RECIST Version 1.1 criteria
Exclusion Criteria:
- Prior or planned allogenic or autologous bone marrow or organ transplantation
- Splenectomy
- Active infection within 1 week of the anticipated first dose of study drug that required antibiotics (or other systemic therapy), physician monitoring or was associated with recurrent fevers (>38.0˚C)
- 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
- Treatment with any live, live-attenuated or COVID-19 vaccine in the 28 days before the first dose of NG-641
- Treatment with any vaccine (including known 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
- 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
- Tumour location/extent considered by the Investigator to present a significant risk if tumour flare or necrosis were to occur
- Use of the following antiviral agents: ribavirin, adefovir, lamivudine or cidofovir within 7 days prior to the first dose of study treatment; or pegylated interferon in the 4 weeks before the first dose of study treatment
- Grade 3 or 4 gastrointestinal bleeding
- Pulmonary embolism, deep vein thrombosis, or other uncontrolled thromboembolic event in the 12 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
- 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.
- 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
- 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 requires treatment. Patients with brain metastases are eligible if these have been treated (surgery, radiotherapy)
- Penetrating tumour infiltration of major blood vessels, pericardium, gastrointestinal tract or other hollow organs that may lead to perforation due to tumour necrosis
- Patients at an increased risk due to tumour flare, as assessed by the Investigator (e.g. an initial increase in tumour size that may lead to intestinal obstruction, obstruction of the ureter or airway)
- Previous treatment with enadenotucirev or FAP targeting agents
- Known allergy to NG-641 transgene products or formulation
- Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
Sites / Locations
- University of Southern California (USC) - Norris Comprehensive Cancer CenterRecruiting
- UCLARecruiting
- Moffitt-Advent Health Clinical Research UnitRecruiting
- Ochsner Medical Center (OMC) - The Gayle and Tom Benson Cancer Center
- Washington University Medical School
- MD Anderson
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intravenous
Arm Description
Phase 1a dose escalation: one cycle of treatment. Phase 1a dose optimisation: up to 8 cycles of treatment
Outcomes
Primary Outcome Measures
Incidence of adverse events (safety and tolerability) in study NG-641
Incidence of adverse events, adverse events meeting protocol-defined DLT criteria, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04053283
Brief Title
First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector
Acronym
STAR
Official Title
A Multicentre, Open-label, Non-randomised First in Human Study of NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector, in Patients With Metastatic or Advanced Epithelial Tumours (STAR)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 23, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akamis Bio
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To characterise the safety and tolerability of NG-641 in patients with metastatic or advanced epithelial tumours.
Detailed Description
To characterise the safety and tolerability of NG-641 in patients with metastatic or advanced epithelial tumours.
The Phase 1a part of the study is a dose-escalation and dose-optimization phase investigating NG-641 administration by intravenous (IV) infusion in a range of tumour types.
The Phase 1b part of the study will investigate the selected optimized multicycle dosing regimen as a monotherapy in up to three cohorts of patients with specific tumour types (Dose Expansion Cohorts A, B and C).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Cancer, Epithelial Tumor
Keywords
metastatic; epithelial; virus; advanced; PsiOxus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
186 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intravenous
Arm Type
Experimental
Arm Description
Phase 1a dose escalation: one cycle of treatment.
Phase 1a dose optimisation: up to 8 cycles of treatment
Intervention Type
Biological
Intervention Name(s)
NG-641
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of adverse events (safety and tolerability) in study NG-641
Description
Incidence of adverse events, adverse events meeting protocol-defined DLT criteria, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death.
Time Frame
End of study treatment visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Phase 1a:
- Histologically or cytologically documented metastatic or advanced epithelial cancer that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available
All patients
Provide written informed consent to participate
At least one measurable site of disease according to RECIST Version 1.1 criteria
Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies
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 or more
Adequate lung reserve
Adequate renal function
Adequate hepatic function
Adequate bone marrow function
Meeting reproductive status requirements
Exclusion Criteria:
Prior or planned allogenic 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 systemic immunosuppressive treatment
Treatment with any live, live-attenuated or COVID-19 vaccine in the 28 days before the first dose of NG-641
Treatment with any vaccine (including known 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 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
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 following prior therapies
Enadenotucirev-based therapy, or a fibroblast activation protein (FAP) targeting agent anytime
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 (PD-1 / PD-L1 therapy permitted without a 'washout' phase)
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-Β (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
Known allergy/immune-related adverse reactions to NG-641 transgene or immune checkpoint inhibitor products or formulation; severe hypersensitivity to another monoclonal antibody
Known hypersensitivity to both cidofovir and valacyclovir
Other prior malignancy active within the previous 3 years (see protocol for exceptions)
Symptomatic brain metastases or any leptomeningeal metastases that are symptomatic and/or requires 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Akamis Bio
Phone
+44 1235835328
Email
enquiries@akamisbio.com
Facility Information:
Facility Name
University of Southern California (USC) - Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gloria Bryant
Phone
323-865-3967
Email
Gloria.Bryant@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Heinz-Josef Lenz
Facility Name
UCLA
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rose Estrada
Email
roserstrada@mednet.ucla.edu
First Name & Middle Initial & Last Name & Degree
Lee Rosen
Facility Name
Moffitt-Advent Health Clinical Research Unit
City
Celebration
State/Province
Florida
ZIP/Postal Code
34747
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Felipe Valerio
Phone
321-460-3580
Email
Felipe.Valerio@AdventHealth.com
First Name & Middle Initial & Last Name & Degree
Guru Sonpavde
Facility Name
Ochsner Medical Center (OMC) - The Gayle and Tom Benson Cancer Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121-2429
Country
United States
Individual Site Status
Completed
Facility Name
Washington University Medical School
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Learn more about this trial
First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector
We'll reach out to this number within 24 hrs