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

• ClinicalTrials.gov Identifier: NCT05165433
• Recruitment Status: Recruiting
• First Posted: December 21, 2021
• Last Update Posted: January 18, 2023
• Sponsor: Akamis Bio
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Akamis Bio

Tracking Information

• First Submitted Date: December 7, 2021
• First Posted Date: December 21, 2021
• Last Update Posted Date: January 18, 2023
• Actual Study Start Date: April 13, 2022
• Estimated Primary Completion Date: March 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2021)

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.

• Original Primary Outcome Measures: Same as current
• 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: Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY)
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Phase 1a will investigate NG-350A administration by intravenous (IV) infusion in combination with fixed-dose pembrolizumab in a range of tumour types. 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
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Epithelial Tumor
• Metastatic Cancer

Intervention

Biological: NG-350A plus Pembrolizumab

Patients receive three doses of NG-350A by intravenous infusion and a single dose of Pembrolizumab by intravenous infusion.

Study Arms

Experimental: All cohorts

NG-350A and pembrolizumab

Intervention: Biological: NG-350A plus Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 7, 2021): 198
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 1, 2023
• Estimated Primary Completion Date: March 1, 2023 (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. One of eleven histologically or cytologically confirmed metastatic/advanced carcinomas or adenocarcinomas that has progressed after at least one line of systemic therapy and are incurable by local therapy
4. At least one measurable site of disease according to RECIST v1.1 criteria
5. Prior treatment with a PD-1/PD-L1 inhibitor
6. Tumour accessible for biopsy, and patient willing to consent to tumour biopsies
7. Ability to comply with study procedures in the Investigator's opinion
8. ECOG performance status 0 or 1
9. Predicted life expectancy of ≥6 months
10. Adequate lung reserve
11. Adequate renal function
12. Adequate hepatic function
13. Adequate bone marrow/haematological function
14. Coagulation profile within the normal range
15. 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 antibiotics, physician monitoring or recurrent fevers (>38.0˚C) associated with a clinical diagnosis of active infection
4. Known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Known history of HIV infection (no testing for HIV, hepatitis B or hepatitis C is required unless mandated by local health authority).
5. Use of the following antiviral agents: ribavirin, adefovir, lamivudine or cidofovir within 10 days prior to the first dose of study treatment; or pegylated interferon (PEG-IFN) in the 4 weeks before the first dose of study treatment
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
11. Lymphangitic carcinomatosis
12. Any of the following in the 3 months before the first dose of study treatment: Grade 3 or 4 gastrointestinal bleeding or risk factors for gastrointestinal bleeding, infectious or inflammatory bowel disease, history or evidence of haemoptysis, significant cardiovascular or cerebrovascular event and any history of bleeding requiring an investigative procedure (e.g. endoscopy), transfusion or hospitalization in the 12 months before the first dose of study treatment
13. Any of the following in the 12 months before the first dose of study treatment: pulmonary embolism, deep vein thrombosis or other uncontrolled thromboembolic event
14. Tumour location/extent considered by the Investigator to present a significant risk of a tumour flare, or necrosis were to occur (e.g. an initial increase in tumour size that may lead to intestinal, airway or ureter obstruction, or penetrating tumour infiltration of major blood vessels, or other hollow organs potentially at risk of perforation)

15. Use of the following prior therapies/treatments:

    1. Treatment with any other enadenotucirev-based virus (parent virus or transgene-modified variants), or anti-CD40 antibody at any time
    2. Radiation therapy to the lung that is >30Gy within 6 months of the first dose of trial treatment
    3. 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)
    4. 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
    5. 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
    6. Bisphosphonate therapy or treatment with Receptor Activator of Nuclear factor Kappa-Β (RANK)-ligand inhibitors for metastatic bone disease is permitted
16. All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to Grade 1 or baseline
17. 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
18. Known allergy or hypersensitivity to NG-350A transgene, pembrolizumab and/or any of its excipients or other monoclonal antibodies
19. 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
20. Known active central nervous system metastases and/or carcinomatous meningitis.
21. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: PsiOxus Therapeutics; +441235835328; enquiries@akamisbio.com

Contact: Pia Donaldson; +441235835328; pia.donaldson@akamisbio.com

• Listed Location Countries: United Kingdom, United States

Administrative Information

• NCT Number: NCT05165433
• Other Study ID Numbers: NG-350A-02
• Has Data Monitoring Committee: No

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
• Current Responsible Party: Akamis Bio
• Original Responsible Party: Same as current
• Current Study Sponsor: Akamis Bio
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: Akamis Bio
• Verification Date: January 2023