Clinical Trials /

First in Human Study With NG-641, an Oncolytic Transgene Expressing Adenoviral Vector

NCT04053283

Description:

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

Related Conditions:
  • Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First in Human Study With NG-641, an Oncolytic Transgene Expressing Adenoviral Vector
  • Official Title: A Multicentre, Open-label, Non-randomised First in Human Study of NG-641, an Oncolytic Transgene Expressing Adenoviral Vector, in Patients With Metastatic or Advanced Epithelial Tumours (STAR)

Clinical Trial IDs

  • ORG STUDY ID: NG-641-01
  • NCT ID: NCT04053283

Conditions

  • Metastatic Cancer
  • Epithelial Tumor

Interventions

DrugSynonymsArms
NG-641Intratumoural
NG-641Intravenous

Purpose

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 Ia part of the study is a dose escalation and dose expansion phase investigating
      NG-641 administration by intratumorural injection (IT) and intravenous (IV) infusion in a
      range of tumour types

      The Phase Ib part of the study is to investigate safety and efficacy of NG-641 as monotherapy
      or in combination with chemotherapy agents and/or checkpoint inhibitors in separate efficacy
      cohorts of patients with specific epithelial tumour types.
    

Trial Arms

NameTypeDescriptionInterventions
IntratumouralExperimentalIn the IT cohort, patients will receive a single dose of NG-641 by IT injection on Day 1. The dose given to each patient will be dependent on the size of the tumour lesion to be injected.
  • NG-641
IntravenousExperimentalIn 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.
  • NG-641

Eligibility Criteria

        Inclusion Criteria:

          1. 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

          2. Provide written informed consent to participate

          3. Aged 18 years or over

          4. a) For patients undergoing surgical excision/resection of tumour lesion(s):

               -  Tumour deemed accessible and safe for biopsy by the Investigator

               -  Patient able to undergo surgical procedure and appropriate anaesthesia

               -  Willing to consent for baseline biopsies and surgical procedure b) For patients
                  not undergoing surgical excision/resection:

               -  Tumour accessible for biopsy and a biopsy deemed safe by the Investigator

               -  Willing to consent to tumour biopsies

          5. ECOG performance status 0 or 1

          6. Predicted life expectancy of 3 months or more

          7. Ability to comply with study procedures in the Investigator's opinion

          8. Adequate renal function

          9. Adequate hepatic function

         10. Adequate bone marrow function

         11. Prothrombin time and aPTT time within normal range and international normalised ratio
             ≤1.5, as appropriate

         12. Meeting reproductive status requirements

         13. Phase Ia - Dose Expansion Phase only: at least one measurable site of disease
             according to RECIST Version 1.1 criteria

        Exclusion Criteria:

          1. Known history or evidence of significant immunodeficiency due to underlying illness

          2. Splenectomy

          3. Active infections requiring antibiotics, physician monitoring or recurrent fevers
             (>38.0˚C) associated with a clinical diagnosis of active infection

          4. 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. Viral serology testing is not required in the absence of history

          5. History of chronic liver disease or evidence of hepatic cirrhosis

          6. History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced),
             organising pneumonia (bronchiolitis obliterans, cryptogenic organising pneumonia,
             etc.)

          7. 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

          8. Incomplete recovery from surgery, incomplete healing of an incision site or evidence
             of infection

          9. Any of the following in the 3 months before the first dose of study treatment: Grade 3
             or 4 gastrointestinal bleeding/haemorrhage (unless due to resected tumour),
             treatment-resistant peptic ulcer disease, erosive oesophagitis or gastritis,
             infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other
             uncontrolled thrombo-embolic event, history or evidence of haemoptysis or menorrhagia

         10. History of myocardial infarction or significant cardiovascular or cerebrovascular
             event in the 6 months before the first dose of study treatment

         11. History of DVT or pulmonary embolus in the 12 months before the first dose of study
             treatment

         12. History of significant bleeding requiring hospitalisation in the 12 months before the
             first dose of study treatment

         13. Patients receiving therapeutic or prophylactic anticoagulation therapy

         14. Treatment with PD-1/programmed death ligand (PD-L1), cytotoxic T-lymphocyte associated
             protein 4 (CTLA-4), or any other (including experimental) immune checkpoint inhibitor
             or immune-stimulatory treatment in the 6 weeks before the first dose of study
             treatment

         15. Major surgery or treatment with any chemotherapy, radiation therapy, biologics for
             cancer or investigational drug/therapy in the 28 days before the first dose of study
             treatment

         16. 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

         17. 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)

         18. Penetrating tumour infiltration of major blood vessels, pericardium, gastrointestinal
             tract or other hollow organs that may lead to perforation due to tumour necrosis

         19. 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)

         20. Lymphangitic carcinomatosis

         21. Any history of renal disease or renal injury, coagulopathy or autoimmune disease

         22. 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

         23. Previous treatment with enadenotucirev or FAP targeting agents

         24. Known allergy to NG-641 transgene products or formulation

         25. Any other medical or psychological condition that would preclude participation in the
             study or compromise ability to give informed consent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (safety and tolerability) in study NG-641
Time Frame:End of study treatment visit, Day 85
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:PsiOxus Therapeutics Ltd

Trial Keywords

  • metastatic; epithelial; virus; advanced

Last Updated