Clinical Trials /

First in Human Study of NG-350A (an Oncolytic Adenoviral Vector Which Expresses an Anti-CD40 Antibody)

NCT03852511

Description:

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 in patients with advanced or metastatic epithelial tumours.

Related Conditions:
  • Adenocarcinoma
  • Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First in Human Study of NG-350A (an Oncolytic Adenoviral Vector Which Expresses an Anti-CD40 Antibody)
  • Official Title: A Multicentre, Open-label, Non Randomised First in Human Study of NG-350A in Patients With Metastatic or Advanced Epithelial Tumours

Clinical Trial IDs

  • ORG STUDY ID: NG-350A-01
  • NCT ID: NCT03852511

Conditions

  • Metastatic Cancer
  • Epithelial Tumor

Interventions

DrugSynonymsArms
NG-350AIntratumoural (Cohort 1)

Purpose

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 in patients with advanced or metastatic epithelial tumours.

Detailed Description

      Phase Ia of this study is a dose escalation and safety expansion phase, investigating NG-350A
      administration by intratumoural (IT) injection and intravenous (IV) infusion. Phase Ib of
      this study will investigate efficacy in patients with specific epithelial tumour types.
    

Trial Arms

NameTypeDescriptionInterventions
Intratumoural (Cohort 1)ExperimentalPatients will receive a single dose of NG-350A by IT injection.
  • NG-350A
Intratumoural (Cohort 2)ExperimentalPatients will receive one cycle of multiple doses of NG-350A by IT injection.
  • NG-350A
IntravenousExperimentalPatients will receive three single doses of NG-350A by IV infusion.
  • NG-350A

Eligibility Criteria

        Inclusion Criteria:

          1. Provide written informed consent to participate

          2. Aged 18 years or over

          3. Histologically or cytologically documented metastatic or advanced epithelial cancer
             (carcinoma or adenocarcinoma) that has relapsed from, or is refractory to, standard
             treatment, or for which no standard treatment is available

          4. a) For patients undergoing surgical excision/resection:

               -  Tumour deemed accessible and safe for biopsy by the Investigator

               -  Willing to consent to biopsies and surgical procedure

               -  Patient able to undergo surgical procedure and appropriate anaesthesia

                  b) For patients not undergoing surgical excision/resection:

               -  Tumour deemed accessible and safe for biopsy by the Investigator

               -  Willing to consent to tumour biopsies

          5. Safety expansion and efficacy cohorts only: at least one measurable site of disease
             according to RECIST criteria.

          6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          7. Predicted life expectancy of 3 months or more

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

          9. Recovered to Grade 1 from the effects (excluding alopecia) of any prior therapy for
             their malignancies

         10. Adequate lung reserve

         11. Adequate renal function

         12. Adequate hepatic function

         13. Adequate bone marrow function

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

         15. Meeting the reproductive requirements of the study

        Exclusion Criteria:

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

          2. Splenectomy

          3. Prior allogeneic or autologous bone marrow or organ transplantation

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

          5. 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 RNA or HCV
             antibody test indicating acute or chronic infection. Positive test for HIV or AIDS;
             testing is not required in the absence of history

          6. 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 14 days before the first dose of study treatment

          7. Administration of an investigational drug in the 28 days, or six half-lives (whichever
             is longer) before the first dose of study treatment

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

          9. 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

         10. Symptomatic brain metastases or any leptomeningeal metastasis that is symptomatic
             and/or requires treatment. Patients with brain metastases are eligible if these have
             been locally treated (surgery, radiotherapy).

         11. Any history of renal disease or renal injury or autoimmune disease.

         12. Any serious or uncontrolled medical disorder that 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

         13. History of myocardial infarction or significant cardiovascular or cerebrovascular
             event in the 12 months before the first dose of study treatment

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

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

         16. Patients receiving therapeutic or prophylactic anticoagulation therapy

         17. Previous treatment with enadenotucirev or an anti-CD40 antibody

         18. Known allergy to NG-350A transgene products or formulation

         19. Any other medical or psychological condition that would preclude participation in the
             study or compromise ability to give informed consent

         20. Patients at an increased risk due to tumour flare

         21. Clinically suspected or radiographic evidence of lymphangitic carcinomatosis

         22. History of idiopathic pulmonary fibrosis, pneumonitis, organising pneumonia, or
             evidence of active pneumonitis

         23. Dependence on supplemental oxygen use

         24. Treatment with any immune checkpoint inhibitors or immune-stimulatory treatment in the
             6 weeks before the first dose of study treatment

         25. Penetrating tumour infiltration of major blood vessels, pericardium, gastrointestinal
             tract or other hollow organs that may lead to perforation due to tumour necrosis
      
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)
Time Frame:Throughout study to end of study treatment visit (Day 57)
Safety Issue:
Description:Characterise the safety and tolerability of NG-350A by reviewing reported Adverse Events (AEs) and Serious Adverse Events (SAEs).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:PsiOxus Therapeutics Ltd

Trial Keywords

  • metastatic; epithelial; virus; advanced

Last Updated

February 6, 2020