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-350AIntravenous

Purpose

This study is to evaluate the safety and tolerability of an oncolytic adenoviral vector which expresses a full length anti-CD40 antibody at the site of virus replication in patients with metastatic or advanced epithelial tumours. 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

      The aim of the study is to characterise the safety and tolerability of NG-350A in patients
      with metastatic or advanced epithelial tumours.

      Phase Ia of the study is a dose escalation and safety expansion phase investigating NG 350A
      administration by intratumoural injection and intravenous infusion. Phase Ib of the study is
      to investigate efficacy 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-350A 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. The total injection volume should be up to a maximum of 2 mL of diluted virus.
  • NG-350A
IntravenousExperimentalIn the IV cohort, patients will receive a single cycle of study treatment, with three single doses of NG-350A on Days 1, 3 and 5 by IV infusion.
  • NG-350A

Eligibility Criteria

        Inclusion Criteria:

          1. Provide written informed consent to participate

          2. Males or females 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:

               -  Excisable tumour/tumour lesion accessible for baseline biopsies and biopsies
                  deemed safe by the Investigator

               -  Willing to consent for baseline biopsies and surgical procedure

               -  Patient able to undergo surgical procedure and appropriate anaesthesia b) For
                  patients not undergoing surgical excision/resection:

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

               -  Willing to consent to tumour biopsies at baseline and during the study

          5. Safety expansion and efficacy cohorts only: at least one measurable site of disease
             according to RECIST criteria; this lesion must be either (i) outside a previously
             irradiated area or (ii) progressive if it is in a previously irradiated area (not
             applicable in patients undergoing surgical excision/resection if the lesion to be
             resected is the target lesion)

          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. Non-impaired renal function

               -  Creatinine ≤1.5 mg/dL and estimated glomerular filtration rate (eGFR) using the
                  Cockroft Gault formula ≥60 mL/min/1.73m2 (or measured creatinine clearance ≥60
                  mL/min)

               -  Urine dipstick for proteinuria at screening and baseline negative or trace.
                  Patients may be included with results of 1+ if they have a spot urinary albumin:
                  creatinine ratio (ACR) of either (i) ≤3 mg/mmol or (ii) >3 mg to <70 mg/mmol with
                  a 24 hour urinary protein <0.2 g/24hours

               -  Serum complement components C3 and C4 above the lower limit of normal range

         11. Adequate hepatic function:

               -  Serum bilirubin <1.5 mg/dL (except patients with Gilbert's syndrome who may have
                  total bilirubin <3.0 mg/mL)

               -  Aspartate aminotransferase and alanine aminotransferase ≤3 x upper limit of
                  normal

               -  Albumin ≥3 g/dL

         12. Adequate bone marrow function:

               -  Absolute neutrophil count ≥1.5 x 109/L

               -  Platelets ≥100 x 109/L

               -  Haemoglobin ≥90 g/L (9 g/dL)

         13. Prothrombin time and activated partial thromboplastin time within normal range or
             international normalised ratio ≤1.5, as appropriate

         14. Meeting reproductive status requirements:

               -  Females must not be pregnant or breastfeeding

               -  Females of childbearing potential must have a negative serum or urine pregnancy
                  test (minimum sensitivity 25 IU/L or equivalent units of human chorionic
                  gonadotrophin [hCG]) within 24 hours before the first dose of study treatment

               -  Females of childbearing potential must agree to use a highly effective method of
                  contraception, for the duration of study treatment with NG-350A and 6 months
                  following the last dose of study treatment. Females of childbearing potential who
                  are continuously not heterosexually active are exempt from contraceptive
                  requirements, but must still undergo pregnancy testing

               -  Fertile males who are sexually active with females of childbearing potential must
                  agree to follow instructions for method(s) of contraception, for the duration of
                  study treatment with NG-350A and 6 months following the last dose of study
                  treatment. In addition, males must be willing to refrain from sperm donation
                  during this time. Azoospermic males are exempt from contraceptive requirements

        Exclusion Criteria:

          1. Known history or evidence of significant immunodeficiency due to underlying illness
             (e.g. human immunodeficiency virus [HIV]/acquired immunodeficiency syndrome [AIDS])
             and/or medication (e.g. systemic corticosteroids or other immunosuppressive
             medications, including cyclosporine, azathioprine, interferons in the 4 weeks before
             the first dose of study treatment). Patients with a condition requiring systemic
             treatment with either corticosteroids (>10 mg daily prednisolone equivalent) or other
             immunosuppressive medications within 14 days of the first dose of study treatment.
             Inhaled or topical steroids and adrenal replacement steroid doses are permitted in the
             absence of autoimmune disease

          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. All toxicities attributed to prior anti-cancer therapy other than alopecia
             must have resolved to Grade 1 or baseline before the first dose of study treatment.
             Patients with toxicities (other than renal toxicities) attributed to prior anti-cancer
             therapy which are not expected to resolve and result in long lasting sequelae, such as
             neuropathy after platinum based therapy, are permitted to enrol

          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). There must also be no requirement for
             immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalent)
             for at least 2 weeks before the first dose of study treatment

         11. Any history of renal disease or renal injury or autoimmune disease. Patients with
             active, known or suspected auto-immune disease or a syndrome that requires systemic or
             immunosuppressive agents; patients with vitiligo, type I diabetes mellitus, residual
             hypothyroidism due to autoimmune disease only requiring hormone replacement, psoriasis
             not requiring systemic treatment or conditions not expected to recur in the absence of
             an external trigger are permitted to enrol providing they comply with the other
             eligibility criteria relating to renal function

         12. 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

         13. History of coagulopathy, transient ischaemic attacks, cerebrovascular accidents or
             venous thromboembolism

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

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

         16. 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-350A-01
Time Frame:End of study treatment visit Day 57
Safety Issue:
Description:Assess the safety and tolerability of NG-350A 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:Recruiting
Lead Sponsor:PsiOxus Therapeutics Ltd

Trial Keywords

  • metastatic; epithelial; virus; advanced

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