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

• ClinicalTrials.gov Identifier: NCT03852511
• Recruitment Status: Recruiting
• First Posted: February 25, 2019
• Last Update Posted: February 7, 2020
• Sponsor: PsiOxus Therapeutics Ltd
• Information provided by (Responsible Party): PsiOxus Therapeutics Ltd

Tracking Information

• First Submitted Date: February 11, 2019
• First Posted Date: February 25, 2019
• Last Update Posted Date: February 7, 2020
• Actual Study Start Date: February 19, 2019
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 21, 2019)

Incidence of adverse events (safety and tolerability) [ Time Frame: Throughout study to end of study treatment visit (Day 57) ]

Characterise the safety and tolerability of NG-350A by reviewing reported Adverse Events (AEs) and Serious Adverse Events (SAEs).

Original Primary Outcome Measures (submitted: February 21, 2019)

Incidence of adverse events (safety and tolerability) in study NG-350A-01 [ Time Frame: End of study treatment visit Day 57 ]

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.

• 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 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
• Brief Summary: 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Metastatic Cancer
• Epithelial Tumor

Intervention

Biological: NG-350A

NG-350A is oncolytic adenoviral vector which expresses a full length agonist anti-CD40 antibody at the site of virus replication.

Study Arms

• Experimental: Intratumoural (Cohort 1)
  Patients will receive a single dose of NG-350A by IT injection.
  Intervention: Biological: NG-350A
• Experimental: Intratumoural (Cohort 2)
  Patients will receive one cycle of multiple doses of NG-350A by IT injection.
  Intervention: Biological: NG-350A
• Experimental: Intravenous
  Patients will receive three single doses of NG-350A by IV infusion.
  Intervention: Biological: NG-350A

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 21, 2019): 125
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2021
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: PsiOxus Therapeutics; +44 1235835328; enquiries@psioxus.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03852511
• Other Study ID Numbers: NG-350A-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
• Responsible Party: PsiOxus Therapeutics Ltd
• Study Sponsor: PsiOxus Therapeutics Ltd
• Collaborators: Not Provided

Investigators

• Principal Investigator: Aung Naing, MD; The University of Texas MD Anderson Cancer Center

• PRS Account: PsiOxus Therapeutics Ltd
• Verification Date: February 2020