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

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)

To characterise the safety and tolerability of NG-641 in patients with metastatic or advanced epithelial tumours.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Cancer; Epithelial Tumor
• Intervention / Treatment: Biological: NG-641

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
• Enrollment (Estimated): 186
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Akamis Bio; Phone Number: +44 1235835328; Email: enquiries@akamisbio.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California (USC) - Norris Comprehensive Cancer Center
      • Principal Investigator: Heinz-Josef Lenz
      • Contact: Gloria Bryant; Phone Number: 323-865-3967; Email: Gloria.Bryant@med.usc.edu
    • Santa Barbara, California, United States, 93105
      • Recruiting
      • UCLA
      • Contact: Rose Estrada; Email: roserstrada@mednet.ucla.edu
      • Principal Investigator: Lee Rosen
  • Florida
    • Celebration, Florida, United States, 34747
      • Recruiting
      • Moffitt-Advent Health Clinical Research Unit
      • Principal Investigator: Guru Sonpavde
      • Contact: Felipe Valerio; Phone Number: 321-460-3580; Email: Felipe.Valerio@AdventHealth.com
  • Louisiana
    • New Orleans, Louisiana, United States, 70121-2429
      • Completed
      • Ochsner Medical Center (OMC) - The Gayle and Tom Benson Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Active, not recruiting
      • Washington University Medical School
  • Texas
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • MD Anderson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

1. Provide written informed consent to participate
2. At least one measurable site of disease according to RECIST Version 1.1 criteria
3. Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies
4. Ability to comply with study procedures in the Investigator's opinion
5. Aged 18 years or over
6. ECOG performance status 0 or 1
7. Predicted life expectancy of 6 months or more
8. Adequate lung reserve
9. Adequate renal function
10. Adequate hepatic function
11. Adequate bone marrow function
12. Meeting reproductive status requirements

Exclusion Criteria:

1. Prior or planned allogenic or autologous bone marrow or organ transplantation
2. Splenectomy
3. 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
4. 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
5. Known history of hepatitis B infection or known active hepatitis C infection. Known history of HIV infection
6. 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
7. Treatment with any live, live-attenuated or COVID-19 vaccine in the 28 days before the first dose of NG-641
8. Treatment with any vaccine (including known non-adenoviral COVID-19 vaccines) in the 7 days before the first dose of NG-641
9. History of prior Grade 3-4 acute kidney injury or other clinically significant renal impairment
10. History of clinically significant interstitial lung disease or non-infectious pneumonitis
11. Lymphangitic carcinomatosis
12. Infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment
13. Any known CTCAE Grade ≥2 coagulation abnormality/coagulopathy
14. Any clinically significant cardiovascular, peripheral vascular, cerebrovascular, or thromboembolic event in the 6 months before the first dose of study treatment
15. 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
16. Tumour location/extent considered by the Investigator to present a significant risk if tumour flare or necrosis were to occur
17. Known retinopathy, including retinal haemorrhages, cotton wool spots, papilloedema, optic neuropathy and retinal artery or vein obstruction
18. Active clinically severe depression

19. 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
20. 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
21. Known allergy/immune-related adverse reactions to NG-641 transgene or immune checkpoint inhibitor products or formulation; severe hypersensitivity to another monoclonal antibody
22. Known hypersensitivity to both cidofovir and valacyclovir
23. Other prior malignancy active within the previous 3 years (see protocol for exceptions)
24. Symptomatic brain metastases or any leptomeningeal metastases that are symptomatic and/or requires treatment
25. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous; Phase 1a dose escalation: one cycle of treatment. Phase 1a dose optimisation: up to 8 cycles of treatment	Biological: NG-641; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	End of study treatment visit

Collaborators and Investigators

• Sponsor: Akamis Bio
• Investigators: Principal Investigator: Haesong Park, MD, Washington University School of Medicine, St Louis, Missouri

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: August 9, 2019
• First Posted (Actual): August 12, 2019

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 19, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: metastatic; epithelial; virus; advanced; PsiOxus
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Neoplasms, Glandular and Epithelial
• Other Study ID Numbers: NG-641-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No