First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector (STAR)

• ClinicalTrials.gov Identifier: NCT04053283
• Recruitment Status: Recruiting
• First Posted: August 12, 2019
• Last Update Posted: January 18, 2023
• Sponsor: Akamis Bio
• Information provided by (Responsible Party): Akamis Bio

Tracking Information

• First Submitted Date: August 9, 2019
• First Posted Date: August 12, 2019
• Last Update Posted Date: January 18, 2023
• Actual Study Start Date: January 23, 2020
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 16, 2023)

Incidence of adverse events (safety and tolerability) in study NG-641 [ Time Frame: End of study treatment visit ]

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.

Original Primary Outcome Measures (submitted: August 9, 2019)

Incidence of adverse events (safety and tolerability) in study NG-641 [ Time Frame: End of study treatment visit, Day 85 ]

Assess the safety and tolerability of NG-641 by review of adverse events including serious adverse events (SAEs), 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.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector
• 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)
• 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).

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Metastatic Cancer
• Epithelial Tumor

Intervention

Biological: NG-641

NG-641 is an oncolytic adenoviral vector which expresses a FAP-TAc antibody together with an immune enhancer module (CXCL9/CXCL10/IFNα).

Study Arms

Experimental: Intravenous

In the IV cohort, patients will receive a single cycle of study treatment, with three single doses of NG-641 on Days 1, 3 and 5 by IV infusion.

Intervention: Biological: NG-641

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 16, 2023): 186
• Original Estimated Enrollment (submitted: August 9, 2019): 42
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Akamis Bio; +44 1235835328; enquiries@akamisbio.com

Contact: Akamis Bio; +44 1235426678; ng64101@akamisbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04053283
• Other Study ID Numbers: NG-641-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Akamis Bio
• Original Responsible Party: Same as current
• Current Study Sponsor: Akamis Bio
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Akamis Bio
• Verification Date: January 2023