Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY) (FORTIFY)

August 1, 2023 updated by: Akamis Bio

A Multicentre, Open-label, Non-randomized, Phase 1a/1b Study of NG-350A, a Tumour-selective Anti-CD40-expressing Adenoviral Vector, in Combination With Pembrolizumab in Patients With Metastatic or Advanced Epithelial Tumours

This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-350A in combination with pembrolizumab in patients with metastatic or advanced epithelial tumours.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Phase 1a will investigate NG-350A administration by intravenous (IV) infusion in combination with fixed-dose pembrolizumab in patients with metastatic or advanced tumours.

Phase 1b will further investigate the efficacy and safety of the selected dose regimen in up to three of the tumour types evaluated in Phase 1a.

Study Type

Interventional

Enrollment (Estimated)

198

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
    • Lancashire
      • Liverpool, Lancashire, United Kingdom, L7 8YA
        • Not yet recruiting
        • The Clatterbridge Cancer Centre Nhs Foundation Trust
        • Principal Investigator:
          • Christian Ottensmeier, MD
        • Contact:
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LE
        • Recruiting
        • Churchill Hospital, Oxford University Hospitals NHS Foundation Trust
        • Principal Investigator:
          • Eileen Parkes, MD
        • Contact:
  • United States
    • California
      • Santa Monica, California, United States, 90404
        • Recruiting
        • UCLA
        • Contact:
        • Principal Investigator:
          • Lee Rosen, MD
      • Santa Monica, California, United States, 90404
        • Not yet recruiting
        • Providence Medical Foundation
        • Contact:
          • Clinical Trials Office
          • Phone Number: 714-446-5177
        • Principal Investigator:
          • David Park, MD
    • Florida
      • Celebration, Florida, United States, 34747
        • Not yet recruiting
        • Moffitt-Advent Health Clinical Research Unit
        • Principal Investigator:
          • Guru Sonpavde, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Aung Naing, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Phase 1a

  1. Patients must have 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.
  2. At least one measurable site of disease according to RECIST v1.1 criteria; this lesion must be either (i) outside a previously irradiated area or (ii) progressive if it is in a previously irradiated area
  3. Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

All patients

  1. Provide written informed consent to participate
  2. Aged 18 years or over on day of signing informed consent
  3. Predicted life expectancy of ≥6 months
  4. Adequate lung reserve
  5. Adequate renal function
  6. Adequate hepatic function
  7. Adequate bone marrow/haematological function
  8. Meeting reproductive status requirements

Exclusion criteria

  1. Prior or planned allogeneic or autologous bone marrow or tissue/organ transplantation
  2. Splenectomy
  3. Active infections requiring systemic anti-infective treatment, physician monitoring/hospital admission 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 autoimmune disease that has required systemic therapy in the past 2 years, are immunocompromised in the opinion of the Investigator, or are receiving chronic systemic immunosuppressive treatment
  7. Treatment with any live, live-attenuated or COVID-19 vaccine in the 30 days before first dose of study drug
  8. Treatment with any other vaccine (including known non live/live-attenuated or non-adenoviral COVID-19 vaccines) in the 7 days before first dose of study drug
  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/interstitial lung disease that required steroids (or current pneumonitis/interstitial lung disease)
  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 (or risk factors for gastrointestinal bleeding), haemoptysis, or any history of bleeding requiring an investigative procedure, transfusion or hospitalization in the 6 months 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. Use of the following prior therapies/treatments :

    • Treatment with any other enadenotucirev-based virus (parent virus or transgene-modified variants), or anti-CD40 antibody at any time
    • Radiation therapy to the lung that is >30Gy within 6 months of the first dose of trial treatment
    • Treatment with an investigational or licensed 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.
    • Prior anti-PD-1 / PD-L1 therapy is permitted without a 'washout' phase
    • Treatment with an investigational or licensed 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
  18. All toxicities attributed to prior anti-cancer therapy must have resolved to Grade 1 or baseline before the first dose of study treatment. (see protocol for exceptions)
  19. Participants with a history of radiation pneumonitis are not eligible for inclusion
  20. Discontinuation from prior treatment with an anti-PD-1 or anti PD L1/PD-L2 agent, or an agent directed to another stimulatory or co-inhibitory T cell receptor, due to a Grade ≥3 immune-related AE
  21. Known allergy or hypersensitivity (Grade ≥3) to NG-350A transgene, pembrolizumab and/or any of its excipients or other monoclonal antibodies
  22. Known hypersensitivity to both cidofovir and valacyclovir
  23. Other prior malignancy active within the previous 3 years (see protocol for exceptions)
  24. Known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and have not required steroid treatment for at least 14 days prior to first dose of study treatment
  25. Positive pregnancy test prior to treatment (a serum test must be performed within 24 hours)
  26. History or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
  27. Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: All cohorts
NG-350A and pembrolizumab
Biological: NG-350A plus Pembrolizumab
Patients receive three doses of NG-350A by intravenous infusion and a single dose of Pembrolizumab by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events (safety and tolerability)
Time Frame: 100 days after last dose of study drug
Assess the safety and tolerability of NG-350A in combination with pembrolizumab by review of adverse events including serious adverse events, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death.
100 days after last dose of study drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Akamis Bio

Collaborators

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 13, 2022

Primary Completion (Estimated)

March 17, 2025

Study Completion (Estimated)

May 23, 2025

Study Registration Dates

First Submitted

December 7, 2021

First Submitted That Met QC Criteria

December 7, 2021

First Posted (Actual)

December 21, 2021

Study Record Updates

Last Update Posted (Actual)

August 2, 2023

Last Update Submitted That Met QC Criteria

August 1, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NG-350A-02

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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